Pathogenesis

The cause of polycystic ovarian syndrome is unknown.

There may be some women who are genetically predisposed to the development of the syndrome (1).

Among women with the syndrome, raised testosterone levels are found in 30% and raised luteinising hormone (LH) levels are found in 40% (2)

It has been proposed that the primary defects in the polycystic ovarian syndrome are:

• insulin resistance in adipose tissue and skeletal muscle
• insulin sensitivity in the ovary

Compensatory hyperinsulinaemia results in androgen secretion by the ovaries. For example, hyperinsulinaemia can stimulate the production of androgens in the ovaries and inhibit the production of sex hormone binding globulin in the liver - these changes can lead to increased serum concentrations of free (active) testosterone.

In women with PCOS, ovarian theca cells seem to be more efficient at converting androgenic precursors to testosterone than are theca cells in unaffected women (3).

Androgens result in the main clinical and endocrine abnormalities.

Women with polycystic ovarian syndrome also are more likely than other women of the same age to have cardiovascular risk factors (central body fat distribution, obesity, hypertension, hypertriglyceridaemia, reduced HDL-cholesterol concentrations). (5)

Women with polycystic ovary syndrome have a 1.3-fold greater risk of developing composite CVD, ischemic heart disease, and stroke compared with women without PCOS. (4,5).

Women with this disorder are also more likely to develop endometrial cancer - one meta-analysis found a 3-fold increased risk of endometrial cancer in PCOS (9% lifetime risk in PCOS versus 3% in unaffected women) (6).

Reference:

1. Goodarzi MO. Looking for polycystic ovary syndrome genes: rational and best strategy. Semin Reprod Med. 2008 Jan;26(1):5-13.
2. Joham AE, Norman RJ, Stener-Victorin E, et al. Polycystic ovary syndrome. Lancet Diabetes Endocrinol. 2022 Sep;10(9):668-80
3. Ehrmann DA. Polycystic ovary syndrome. NEJM 2005;352:1223-36
4. Okoth K, Chandan JS, Marshall T, et al. Association between the reproductive health of young women and cardiovascular disease in later life: umbrella review. BMJ. 2020 Oct 7;371:m3502.
5. Zhao L, Zhu Z, Lou H, et al. Polycystic ovary syndrome (PCOS) and the risk of coronary heart disease (CHD): a meta-analysis. Oncotarget. 2016 Jun 7;7(23):33715-21.
6. Haoula Z, Salman M, Atiomo W. Evaluating the association between endometrial cancer and polycystic ovary syndrome. Hum Reprod. 2012 May;27(5):1327-31.